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1.
Increased chronic lymphocytic leukemia proliferation upon IgM stimulation is sustained by the upregulation of miR‐132 and miR‐212
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Sabina Chiaretti Nadia Peragine Valerio Fulci Maria R. Ricciardi Monica Messina Silvia Bonina Fulvia Brugnoletti Marilisa Marinelli Valeria Di Maio Francesca R. Mauro Ilaria Del Giudice Giuseppe Macino Anna Guarini 《Genes, chromosomes & cancer》2015,54(4):222-234
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Smaller inner ear sensory epithelia in Neurog 1 null mice are related to earlier hair cell cycle exit. 总被引:4,自引:0,他引:4
V Matei S Pauley S Kaing D Rowitch K W Beisel K Morris F Feng K Jones J Lee B Fritzsch 《Developmental dynamics》2005,234(3):633-650
We investigated whether co-expression of Neurog 1 and Atoh 1 in common neurosensory precursors could explain the loss of hair cells in Neurog 1 null mice. Analysis of terminal mitosis, using BrdU, supports previous findings regarding timing of exit from cell cycle. Specifically, we show that cell cycle exit occurs in spiral sensory neurons in a base-to-apex progression followed by cell cycle exit of hair cells in the organ of Corti in an apex-to-base progression, with some overlap of cell cycle exit in the apex for both hair cells and spiral sensory neurons. Hair cells in Neurog 1 null mice show cell cycle exit in an apex-to-base progression about 1-2 days earlier. Atoh 1 is expressed in an apex-to-base progression rather then a base-to-apex progression as in wildtype littermates. We tested the possible expression of Atoh1 in neurosensory precursors using two Atoh 1-Cre lines. We show Atoh 1-Cre mediated beta-galactosidase expression in delaminating sensory neuron precursors as well as undifferentiated epithelial cells at E11 and E12.5. PCR analysis shows expression of Atoh 1 in the otocyst as early as E10.5, prior to any histology-based detection techniques. Combined, these data suggest that low levels of Atoh 1 exist much earlier in precursors of hair cells and sensory neurons, possibly including neurosensory precursors. Analysis of Atoh 1-Cre expression in E18.5 embryos and P31 mice reveal beta-galactosidase stain in all hair cells but also in vestibular and cochlear sensory neurons and some supporting cells. A similar expression of Atoh 1-LacZ exists in postnatal and adult vestibular and cochlear sensory neurons, and Atoh 1 expression in vestibular sensory neurons is confirmed with RT-PCR. We propose that the absence of NEUROG 1 protein leads to loss of sensory neuron formation through a phenotypic switch of cycling neurosensory precursors from sensory neuron to hair cell fate. Neurog 1 null mice show a truncation of clonal expansion of hair cell precursors through temporally altered terminal mitosis, thereby resulting in smaller sensory epithelia. 相似文献
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Basic helix-loop-helix gene Hes6 delineates the sensory hair cell lineage in the inner ear. 总被引:1,自引:0,他引:1
Dong Qian Kristen Radde-Gallwitz Michael Kelly Bj?rn Tyrberg Jaesang Kim Wei-Qiang Gao Ping Chen 《Developmental dynamics》2006,235(6):1689-1700
The basic helix-loop-helix (bHLH) gene Hes6 is known to promote neural differentiation in vitro. Here, we report the expression and functional studies of Hes6 in the inner ear. The expression of Hes6 appears to be parallel to that of Math1 (also known as Atoh1), a bHLH gene necessary and sufficient for hair cell differentiation. Hes6 is expressed initially in the presumptive hair cell precursors in the cochlea. Subsequently, the expression of Hes6 is restricted to morphologically differentiated hair cells. Similarly, the expression of Hes6 in the vestibule is in the hair cell lineage. Hes6 is dispensable for hair cell differentiation, and its expression in inner ear hair cells is abolished in the Math1-null animals. Furthermore, the introduction of Hes6 into the cochlea in vitro is not sufficient to promote sensory or neuronal differentiation. Therefore, Hes6 is downstream of Math1 and its expression in the inner ear delineates the sensory lineage. However, the role of Hes6 in the inner ear remains elusive. 相似文献
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Zhiyong Liu Thomas Owen Jie Fang R. Sathish Srinivasan Jian Zuo 《Developmental dynamics》2012,241(10)
COVER PHOTOGRAPH: Lineage tracing of Prox1 expressing inner ear cochlear cells in Prox1CreEGFP/+; Rosa26‐EYFPloxp/+ mice at P23. All cochlear hair cells are labeled with calbindin in red. EYFP in green historically records the cochlear cells experiencing Prox1 expression during the development, which include hair cells and supporting cells (both inside and outside the organ of Corti). From Liu et al., Developmental Dynamics 241:684–696, 2012. 相似文献
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Overexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears 总被引:17,自引:0,他引:17
For mammalian cochlear hair cells, fate determination is normally completed by birth. We report here that overexpression of Math1, a mouse homolog of the Drosophila gene atonal, in postnatal rat cochlear explant cultures resulted in extra hair cells. Surprisingly, we found that the source of the ectopic hair cells was columnar epithelial cells located outside the sensory epithelium in the greater epithelial ridge, which normally give rise to inner sulcus cells. Moreover, Math1 expression also facilitated conversion of postnatal utricular supporting cells into hair cells. Thus Math1 was sufficient for the production of hair cells in the ear, and immature postnatal mammalian inner ears retained the competence to generate new hair cells. 相似文献
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Gerben Duns Anke van den Berg Marcory C. R. F. van Dijk Inge van Duivenbode Cor Giezen Joost Kluiver Harry van Goor Robert M. W. Hofstra Eva van den Berg Klaas Kok 《Genes, chromosomes & cancer》2013,52(2):165-173
Despite numerous studies reporting deregulated microRNA (miRNA) and gene expression patterns in clear cell renal cell carcinoma (ccRCC), no direct comparisons have been made to its presumed normal counterpart: the renal proximal tubular epithelial cells (PTECs). The aim of this study was to determine the miRNA expression profiles of 10 ccRCC‐derived cell lines and short‐term cultures of PTEC and to correlate these with their gene expression and copy‐number profiles. Using microarray‐based methods, a significantly altered expression level in ccRCC cell lines was observed for 23 miRNAs and 1630 genes. The set of miRNAs with significantly decreased expression levels include all members of the miR‐200 family known to be involved in the epithelial to mesenchymal transition process. Expression levels of 13 of the 47 validated target genes for the downregulated miRNAs were increased more than twofold. Our data reinforce the importance of the epithelial to mesenchymal transition process in the development of ccRCC. © 2012 Wiley Periodicals, Inc. 相似文献
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Florian Haller Anja von Heydebreck Jitao David Zhang Bastian Gunawan Claus Langer Giuliano Ramadori Stefan Wiemann
zgür Sahin 《The Journal of pathology》2010,220(1):71-86
The molecular biology and clinical behaviour of gastrointestinal stromal tumours (GISTs) are associated with their anatomical localization (stomach or intestine), and also with the mutation status of the receptor tyrosine kinases KIT and PDGFRA. Twelve GISTs were evaluated for differential miRNA expression signatures by use of microarrays representing 734 human miRNAs. Thirty‐two miRNAs were found to be differentially expressed according to localization and mutation status. Differential expression was further analysed and confirmed for four miRNAs (miR‐132, miR‐221, miR‐222, and miR‐504) by qRT‐PCR in 49 additional GISTs. Differentially expressed miRNAs were functionally mapped to KIT/PDGFRA signalling and G1/S‐phase transition of the cell cycle, revealing 22 predicted miRNA/mRNA interactions for ten gene targets from KIT/PDGFRA signalling, and 12 interactions for 12 gene targets of G1/S‐phase transition. Moreover, the expression of 44 miRNAs clustered in a genetically imprinted region at 14q32.31 was found to be strongly correlated in the microarray analysis. This was confirmed for two selected miRNAs (miR‐134 and miR‐370) from the 14q32.31 cluster by qRT‐PCR in 49 additional GISTs, and the expression of these two miRNAs was significantly lower in GISTs with 14q loss, and also in GISTs with tumour progress. miRNA profiling may prove to be a key determinant of the biology and clinical features of GISTs Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
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Toshinori Hayashi Dale Cunningham Olivia Bermingham-McDonogh 《Developmental dynamics》2007,236(2):525-533
Previous studies have demonstrated the importance of FGF signaling at several stages in the development of the cochlea. At early stages of embryogenesis, Fgfr1, Fgfr2, and several FGFs are critical for both the induction of the otic vesicle and the initial development of the sensory epithelium. At late stages of cochlear development, Fgfr3 is necessary for the development of the tunnel of Corti. To determine the stage of development when Fgfr3 is required, we examined the expression of Fgfr3 and Fgf8 at various developmental stages. We also re-examined the Fgfr3 -/- mouse with additional markers for developing supporting cells. We confirmed the previous analysis of the Fgfr3 -/- mice, indicating that there are deficiencies in support cell differentiation. Specifically, we find that the inner pillar cell never develops, while the outer pillar cell is stalled in its differentiation. In addition, we found an extra row of outer hair cells, and accompanying Deiters' cells, in the apical two thirds of the organ of Corti in the Fgfr3 mutant. Thus, in addition to controlling the fate decision between pillar cells and Deiters' cells, we find that Fgfr3 also regulates the width of the sensory epithelium. 相似文献
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Mohamed Guled Leo Lahti Pamela M. Lindholm Kaisa Salmenkivi Izhar Bagwan Andrew G. Nicholson Sakari Knuutila 《Genes, chromosomes & cancer》2009,48(7):615-623
Malignant mesothelioma (MM) is an aggressive cancer arising from mesothelial cells, mainly due to former asbestos exposure. Little is known about the microRNA (miRNA) expression of MM. miRNAs are small noncoding RNAs, which play an essential role in the regulation of gene expression. This study was carried out to analyze the miRNA expression profile of 17 MM samples using miRNA microarray. The analysis distinguished the overall miRNA expression profiles of tumor tissue and normal mesothelium. Differentially expressed miRNAs were found in tumor samples compared with normal sample. Twelve of them, let‐7b*, miR‐1228*, miR‐195*, miR‐30b*, miR‐32*, miR‐345, miR‐483‐3p, miR‐584, miR‐595, miR‐615‐3p, and miR‐885‐3p, were highly expressed whereas the remaining nine, let‐7e*, miR‐144*, miR‐203, miR‐340*, miR‐34a*, miR‐423, miR‐582, miR‐7‐1*, and miR‐9, were unexpressed or had severely reduced expression levels. Target genes for these miRNAs include the most frequently affected genes in MM such as CDKN2A, NF2, JUN, HGF, and PDGFA. Many of the miRNAs were located in chromosomal areas known to be deleted or gained in MM such as 8q24, 1p36, and 14q32. Furthermore, we could identify specific miRNAs for each histopathological subtype of MM. Regarding risk factors such as smoking status and asbestos exposure, significantly differentially expressed miRNAs were identified in smokers versus nonsmokers (miR‐379, miR‐301a, miR‐299‐3p, miR‐455‐3p, and miR‐127‐3p), but not in asbestos‐exposed patients versus nonexposed ones. This could be related to the method of assessment of asbestos exposure as asbestos remains to be the main contributor to the development of MM. © 2009 Wiley‐Liss,Inc. 相似文献
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Chan Ho Hwang Dayong Guo Marie A. Harris Omar Howard Yuji Mishina Lin Gan Stephen E. Harris Doris K. Wu 《Developmental dynamics》2010,239(2):505-513
The mammalian organ of Corti of the inner ear is a highly sophisticated sensory end organ responsible for detecting sound. Noggin is a secreted glycoprotein, which antagonizes bone morphogenetic proteins 2 and 4 (Bmp2 and Bmp4). The lack of this antagonist causes increased rows of inner and outer hair cells in the organ of Corti. In mice, Bmp2 is expressed transiently in nascent cochlear hair cells. To investigate whether Noggin normally modulates the levels of Bmp2 for hair cell formation, we deleted Bmp2 in the cochlear hair cells using two cre strains, Foxg1cre/+ and Gfi1cre/+. Bmp2 conditional knockout cochleae generated using these two cre strains show normal hair cells. Furthermore, Gfi1cre/+;Bmp2lox/? mice are viable and have largely normal hearing. The combined results of Noggin and Bmp2 mutants suggest that Noggin is likely to regulate other Bmps in the cochlea such as Bmp4. Developmental Dynamics 239:505–513, 2010. Published 2010 Wiley‐Liss, Inc. 相似文献
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Adolfo B. Frias Jr Heather M. Buechel Arpan Neupane Louise M. D'Cruz 《Immunology》2018,153(2):238-245
Invariant natural killer T (iNKT) cells are adaptive T cells with innate‐like characteristics including rapid cytokine production and a proliferative response to stimulation. Development of these cells in the thymus is dependent on expression of the microRNA (miRNA) processing enzyme Dicer, indicating that iNKT cells probably have distinct miRNA requirements for gene regulation during development. The miRNA miR‐155 has previously been shown to have numerous roles in T cells, including regulation of proliferation and differentiation, and positive modulation of interferon‐γ expression. We examined the role of miR‐155 in the development and function of iNKT cells. Using germline‐deficient miR‐155 mice, we showed that loss of miR‐155 resulted in unchanged iNKT cell frequency and cell number. Although miR‐155 was up‐regulated in iNKT cells upon activation with α‐galactosylceramide, loss of miR‐155 did not affect cytokine production or proliferation by iNKT cells. Hence, cytokine production occurs in iNKT cells independently of miR‐155 expression. 相似文献
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MicroRNAs regulate T‐cell production of interleukin‐9 and identify hypoxia‐inducible factor‐2α as an important regulator of T helper 9 and regulatory T‐cell differentiation
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MicroRNAs (miRNAs) regulate many aspects of helper T cell (Th) development and function. Here we found that they are required for the suppression of interleukin‐9 (IL‐9) expression in Th9 cells and other Th subsets. Two highly related miRNAs (miR‐15b and miR‐16) that we previously found to play an important role in regulatory T (Treg) cell differentiation were capable of suppressing IL‐9 expression when they were over‐expressed in Th9 cells. We used these miRNAs as tools to identify novel regulators of IL‐9 expression and found that they could regulate the expression of Epas1, which encodes hypoxia‐inducible factor (HIF)‐2α. HIF proteins regulate metabolic pathway usage that is important in determining appropriate Th differentiation. The related protein, HIF‐1α enhances Th17 differentiation and inhibits Treg cell differentiation. Here we found that HIF‐2α was required for IL‐9 expression in Th9 cells, but its expression was not sufficient in other Th subsets. Furthermore, HIF‐2α suppressed Treg cell differentiation like HIF‐1α, demonstrating both similar and distinct roles of the HIF proteins in Th differentiation and adding a further dimension to their function. Ironically, even though miR‐15b and miR‐16 suppressed HIF‐2α expression in Treg cells, inhibiting their function in Treg cells did not lead to an increase in IL‐9 expression. Therefore, the physiologically relevant miRNAs that regulate IL‐9 expression in Treg cells and other subsets remain unknown. Nevertheless, the analysis of miR‐15b and miR‐16 function led to the discovery of the importance of HIF‐2α so this work demonstrated the utility of studying miRNA function to identify novel regulatory pathways in helper T‐cell development. 相似文献
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M Renner E Czwan W Hartmann R Penzel B Brors R Eils E Wardelmann R Büttner P Lichter P Schirmacher G Mechtersheimer 《Genes, chromosomes & cancer》2012,51(11):982-996
High‐grade soft tissue sarcomas are a heterogeneous and complex group of tumors. MicroRNAs (miRNAs) are considered as attractive candidates that may improve diagnostic, prognostic, and predictive characterization of this group of malignancies. We performed a comprehensive miRNA expression analysis in a series of 76 untreated, primary high‐grade soft tissue sarcomas representing eight subtypes, and in a panel of 15 representative sarcoma cell lines using microarray technology. This screening revealed unique miRNA expression patterns for synovial sarcomas, myxoid liposarcomas, and leiomyosarcomas, and defined unique sets of miRNAs discriminating the different liposarcoma subtypes from non‐neoplastic adipose tissue. The over‐represented miRNAs included members of the miR‐200 family in synovial sarcomas, and the tumor‐associated miR‐9 and miR‐9* in myxoid liposarcomas compared to adipose tissue. Moreover, we found coexpression of 63 miRNAs clustering in a genetically imprinted chromosomal region 14q32.2 separating primary sarcoma samples and sarcoma cell lines into two molecular subgroups. Taken together, our comprehensive miRNA profiling identified a novel set of miRNAs that might contribute to sarcomagenesis and provide a starting point for experimental modulation of relevant targets for new therapeutic strategies in high‐grade sarcomas. © 2012 Wiley Periodicals, Inc. 相似文献
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Raffaele Baffa Matteo Fassan Stefano Volinia Brian O'Hara Chang‐Gong Liu Juan P Palazzo Marina Gardiman Massimo Rugge Leonard G Gomella Carlo M Croce Anne Rosenberg 《The Journal of pathology》2009,219(2):214-221
Small non‐coding microRNAs (miRNAs) contribute to cancer development and progression, and are differentially expressed in normal tissues and cancers. However, the specific role of miRNAs in the metastatic process is still unknown. To seek a specific miRNA expression signature characterizing the metastatic phenotype of solid tumours, we performed a miRNA microarray analysis on 43 paired primary tumours (ten colon, ten bladder, 13 breast, and ten lung cancers) and one of their related metastatic lymph nodes. We identified a metastatic cancer miRNA signature comprising 15 overexpressed and 17 underexpressed miRNAs. Our results were confirmed by qRT‐PCR analysis. Among the miRNAs identified, some have a well‐characterized association with cancer progression, eg miR‐10b, miR‐21, miR‐30a, miR‐30e, miR‐125b, miR‐141, miR‐200b, miR‐200c, and miR‐205. To further support our data, we performed an immunohistochemical analysis for three well‐defined miRNA gene targets (PDCD4, DHFR, and HOXD10 genes) on a small series of paired colon, breast, and bladder cancers, and one of their metastatic lymph nodes. We found that the immunohistochemical expression of these targets significantly follows the corresponding miRNA deregulation. Our results suggest that specific miRNAs may be directly involved in cancer metastasis and that they may represent a novel diagnostic tool in the characterization of metastatic cancer gene targets. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献